One of the critical requirements for the success of this program will be the ability to identify heterozygous p53 mutations in the constitutional tissues of probands and their families. The foundation of this program is the examination of relatively large numbers of samples for what could be many different single base mutations. The success of this project requires the accurate and rapid identification of mutations in the p53 gene from either constitutional or tumor tissues. This core has been proposed to develop the techniques necessary to identify these mutations, and then to examine the probands or nearest affected relatives from the cohorts to determine the frequency of p53 mutations in these families and individuals.